The Scripps NeuroAIDS Preclinical Studies (SNAPS) Center was organized in 2000 in order to promote the innovative and highly productive cross-disciplinary research program at The Scripps Research Institute (TSRI) that focused on modeling the untoward effects of HIV in the central nervous system (CNS). Significant success has been achieved, with the SNAPS NIMH P30 Center providing leadership and support for multiple investigators from many fields of inquiry through its activities and Cores. This has resulted, to date, in 138 original research publications and numerous interdisciplinary collaborations. Here, we present our plans to renew the Center. Studies from the SNAPS Center, those of others, and the new clinical findings in neuroAIDS lead us to propose new and restructured Cores. These capitalize on state of the art scientific advances, illustrative in vivo and in vitro systems, and now, building on our preclinical basic science success, direct links and projects with clinical researchers to analyze clinical specimens. We will insure a strong focus on the problems of neuroAIDS. Three themes: Virus-Host Interactions, Integrative Neuropathogenesis, and Discovery, provide the basis for the research, which are united under a systems biology approach to understand the current and changing dynamics of neuroAIDS. The four Research Cores, a single Developmental Core, and an Administrative Core will serve key roles in unraveling the complexity of neuroAIDS. The organization and communication among investigators under the auspices of the SNAPS has, and is expected to continue to, foster numerous other spin-off projects/grants, and to provide training, mentoring, and resources for neuroAIDS work. Additional, open access databases and bioinformatic tools will be made available to the scientific community as a whole, aiding in the efforts to prevent and/or treat this devastating condition.